Trana Discovery provides a proprietary drug discovery technology platform that enables its partners to discover new treatments of bacterial, viral, and fungal infectious diseases. Our assays screen compounds to identify potential drug candidates that work through a novel mechanism of action: inhibition of the target pathogen(s) ability to use an organism-specific transfer RNA (tRNA), essential for propagation.
The lead assay platform offered by Trana Discovery can screen for potential inhibitors of HIV replication by identifying compounds that inhibit the virus’s ability to use tRNA Lysine. This step is critical for the virus to create new virus and thereby inhibits the spread to uninfected cells. Working with Southern Research, Trana has developed an assay platform that can screen 50,000 compounds per day.
The tRNA Mechanism of Action
Scientists at North Carolina State University have long understood the crucial role of transfer RNA (tRNA). All organisms need tRNA for normal protein synthesis. Specifically in HIV, the virus uses human tRNALys3SUU from the host cell to form complexes with the HIV genome RNA during replication. Inhibition of tRNA during RNA replication or blocking its recruitment during assembly should stop the replicative cycle, and the virus would not be able to survive.
Founders of Trana Discovery helped characterize the structure tRNA, particularly of the ultra conserved region, the anti-codon stem loop (ASL), of this complex protein. Chemicals that bind to these regions could be identified, thereby inhibiting the action of tRNA, new drugs could be crafted for use in treating human and animal diseases.
Trana Discovery technology exploits this conserved region of tRNA through the following illustration. As infectious organisms are selected as targets, a unique probe, based on a pre-determined sequence, is developed to mimic the chemical structures of the ASL. The probe is then employed in a high-throughput screening process to identify compounds that react with high affinity and inextricably bind to the ASL, indicating discovery of a molecule that possesses tRNA inhibitory activity specific to the target pathogen. By inhibiting the role of tRNA and crippling protein assembly, protein synthesis cannot proceed, thus stopping pathogen growth and spread of infection. Because each pathogen uses a unique combination of tRNA, a wide range of compounds with targeted anti-infective characteristics is possible.
Scientific and Business Value
Scientists who employ Trana Discovery technology can stay on the forefront of scientific discovery and make significant scientific contributions in the fields of infectious disease and biochemistry. The Trana Discovery technology enables teams to discover new applications for existing drug compound libraries that they might have otherwise been missed using traditional screening assays. Trana Discovery technology can help to increase success rates and expedite discovery of lead drug candidates by demonstrating, quantifying, and validating the mechanism of action. Organizations that use Trana Discovery technology can progress drugs to their development pipeline more efficiently.